Flavonoids inhibit the amidolytic activity of human thrombin

Mozzicafreddo, Matteo; Cuccioloni, Massimiliano; Eleuteri, Anna Maria; Fioretti, Evandro; Angeletti, Mauro

doi:10.1016/j.biochi.2006.04.007

Cited by 48 publications

(57 citation statements)

References 83 publications

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“…This might be due to the presence of high percentage of phenolic acids in F3. Phenolic acids together with carbohydrates and uronic acids had been suggested to play a role in anticoagulant activities by Pawlaczyk et al [17, 18] and Mozzicafreddo et al [19]. …”

Section: Resultsmentioning

confidence: 99%

“…Even though the hexuronic acid and polysaccharides contents were moderate for F3, its anticoagulant activity is still promising. Mozzicafreddo et al [19], Guglielmone et al [28], and Dong et al [29] reported that polyphenolic demonstrated anticoagulant activity through prolongation of activated partial thromboplastin time (APTT). In this regard, we postulate that probably the anticoagulant activity of F3 could be due to its high polyphenolic contents.…”

Section: Resultsmentioning

confidence: 99%

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Anticoagulant Activity of Polyphenolic‐Polysaccharides Isolated from Melastoma malabathricum L.

Khoo

Abas

Abdullah

et al. 2014

Evidence-Based Complementary and Alternative Medicine

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Melastoma malabathricum Linn. is a perennial traditional medicine plants that grows abundantly throughout Asian countries. In this study, M. malabathricum Linn. leaf hot water crude extract with anticoagulant activity was purified through solid phase extraction cartridge and examined for the bioactive chemical constituents on blood coagulation reaction. The SPE purified fractions were, respectively, designated as F1, F2, F3, and F4, and each was subjected to the activated partial thromboplastin time (APTT) anticoagulant assay. Active anticoagulant fractions (F1, F2, and F3) were subjected to chemical characterisation evaluation. Besides, neutral sugar for carbohydrate part was also examined. F1, F2, and F3 were found to significantly prolong the anticoagulant activities in the following order, F1 > F2 > F3, in a dose dependent manner. In addition, carbohydrate, hexuronic acid, and polyphenolic moiety were measured for the active anticoagulant fractions (F1, F2, and F3). The characterisation of chemical constituents revealed that all these three fractions contained acidic polysaccharides (rhamnogalacturonan, homogalacturonan, and rhamnose hexose-pectic type polysaccharide) and polyphenolics. Hence, it was concluded that the presence of high hexuronic acids and polysaccharides, as well as polyphenolics in traditional medicinal plant, M. malabathricum, played a role in prolonging blood clotting in the intrinsic pathway.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Anticoagulant Activity of Polyphenolic‐Polysaccharides Isolated from Melastoma malabathricum L.

Khoo

Abas

Abdullah

et al. 2014

Evidence-Based Complementary and Alternative Medicine

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“…Dabigratan is an oral DTI licensed for the prevention of thromboembolism and stroke worldwide [26,27] but it is still not known how long it will be effective, as side effects and resistance have been described for some anticoagulant/antiplatelet molecules after long periods of use (e.g., acetyl salicylic acid and clopidogrel) [28,29,30]. …”

Section: Resultsmentioning

confidence: 99%

“…Moreover, thrombin inhibition has also been shown to be positively correlated to the number of hydroxyl groups present in the flavonoid moiety [38]. This particular feature has been correlated with the inhibition of multi-subunit proteases complex such as the proteasome [36] and smaller serine proteases such as thrombin and Dengue virus NS2B-S3 [28,39]. …”

Section: Resultsmentioning

confidence: 99%

Marine Diterpenes: Molecular Modeling of Thrombin Inhibitors with Potential Biotechnological Application as an Antithrombotic

et al. 2017

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Thrombosis related diseases are among the main causes of death and incapacity in the world. Despite the existence of antithrombotic agents available for therapy, they still present adverse effects like hemorrhagic risks which justify the search for new options. Recently, pachydictyol A, isopachydictyol A, and dichotomanol, three diterpenes isolated from Brazilian marine brown alga Dictyota menstrualis were identified as potent antithrombotic molecules through inhibition of thrombin, a key enzyme of coagulation cascade and a platelet agonist. Due to the biotechnological potential of these marine metabolites, in this work we evaluated their binding mode to thrombin in silico and identified structural features related to the activity in order to characterize their molecular mechanism. According to our theoretical studies including structure-activity relationship and molecular docking analysis, the highest dipole moment, polar surface area, and lowest electronic density of dichotomanol are probably involved in its higher inhibition percentage towards thrombin catalytic activity compared to pachydictyol A and isopachydictyol A. Interestingly, the molecular docking studies also revealed a good shape complementarity of pachydictyol A and isopachydictyol A and interactions with important residues and regions (e.g., H57, S195, W215, G216, and loop-60), which probably justify their thrombin inhibitor effects demonstrated in vitro. Finally, this study explored the structural features and binding mode of these three diterpenes in thrombin which reinforced their potential to be further explored and may help in the design of new antithrombotic agents.

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“…Many publications document that fl avonoids, a class of natural polyphenolic substances, also possess inhibitory effect on various enzymes including serine proteases. They are effective in inhibition of serine proteases like trypsin (Parellada and Guinea, 1995;Maliar et al, 2004;Jedinák et al, 2006;Shahwar et al, 2012), thrombin (Jedinák et al, 2006;Mozzicafreddo et al, 2006;Liu et al, 2010), urokinase (Devipriya et al, 2006;Jedinák et al, 2006) or elastase (Kanashiro et al, 2007;Krenn et al, 2009;Philips et al, 2010). Among tested fl avonoids quercetin exhibited the best inhibitory action on trypsin, thrombin and elastase (Maliar et al, 2004;Mozzicafreddo et al, 2006;Kanashiro et al, 2007).…”

Section: Introductionmentioning

confidence: 94%

Inhibition of pathophysiological proteases with novel quercetin derivatives

Danihelová

Veverka²,

Šturdı́k³

2013

Acta Chimica Slovaca

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Novel quercetin derivatives were prepared to change its physicochemical properties and effects on activity of proteolytic enzymes. For them preparation, the selective protection procedures some of the quercetin hydroxyl groups and acylation of the others with acylchlorides were used. The ability of these compounds to inhibit the activity of serine proteases e.g. trypsin, thrombin, urokinase and elastase was studied. In micromolar range, tested derivatives were the most potent inhibitors of thrombin. There was estimated better inhibition of thrombin for prenylated, acetylated, feruloyl and caffeoyl quercetin esters. Slight inhibitory effect of all quercetin derivatives on elastase was found. Among tested derivatives only diquercetin displayed better inhibiton. Trypsin and urokinase were inhibited by quercetin at comparable level. Slight improvement in inhibitory effect of trypsin and urokinase was seen for chloronaphtoquinone quercetin that revealed enhanced inhibiton of thrombin, too. However, no infl uence on elastase activity was determined for this compound. Obtained results indicate that certain modifi cations of quercetin structure could improve its biological properties.

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Flavonoids inhibit the amidolytic activity of human thrombin

Cited by 48 publications

References 83 publications

Anticoagulant Activity of Polyphenolic‐Polysaccharides Isolated from Melastoma malabathricum L.

Anticoagulant Activity of Polyphenolic‐Polysaccharides Isolated from Melastoma malabathricum L.

Marine Diterpenes: Molecular Modeling of Thrombin Inhibitors with Potential Biotechnological Application as an Antithrombotic

Inhibition of pathophysiological proteases with novel quercetin derivatives

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